RECOVER-ENERGIZE Platform Protocol_Appendix A (Exercise Intolerance)

NCT06404060 | Active Not Recruiting DMC

• 3 other identifiers: Pro00112409_AOT2HL156812NHLBI Grant to RTI
• Study Type: interventional
• Target: 360
• Locations: 1 country
• Sites: 1

Brief Summary

This is a platform protocol designed to be flexible so that it is suitable for a range of interventions and settings within diverse health care systems and community settings with incorporation into clinical COVID-19 management programs and treatment plans if results achieve key study outcomes. This protocol is a prospective, multi-center, multi-arm, randomized, controlled platform trial evaluating interventions to address and improve exercise intolerance and post-exertional malaise (PEM) as manifestations of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC). The focus of this protocol is to assess interventions that can improve exercise capacity, daily activities tolerance, and quality of life in patients with PASC.

Conditions

Long Covid-19; Long COVID

Keywords

PASC; Exercise; PEM (post exertional malaise)

Outcome Measures

Primary Outcomes (1)

• Change in Endurance Shuttle Walk Test (ESWT)

  The ESWT consists of timed walking on a 10m course. The result is expressed as total walking time after an initial 2-minute warm-up. The ESWT is an outcome measure of exercise capacity.

  Baseline, week 12 (End of Intervention (EOI))

Secondary Outcomes (5)

• Change in physical function, as measured by the PROMIS SF-Physical Function (PROMIS-PF)

  Baseline, week 6 (middle of intervention), week 12 (EOI) and week 24 End of Study (EOS)

• Change in physical function, as measured by actigraphy

  Baseline, week 6 (middle of intervention), week 12 (EOI) and week 24 End of Study (EOS)

• Change in symptom frequency, as measured by the Modified DePaul Symptom Questionnaire - Post-Exertional Malaise (mDSQ-PEM)

  Baseline, week 6 (middle of intervention), week 12 (EOI) and week 24 End of Study (EOS)

• Change in symptom severity, as measured by the Modified DePaul Symptom Questionnaire - Post-Exertional Malaise (mDSQ-PEM)

  Baseline, week 6 (middle of intervention), week 12 (EOI) and week 24 End of Study (EOS)

• Change in symptom duration, as measured by the Modified DePaul Symptom Questionnaire - Post-Exertional Malaise (mDSQ-PEM)

  Baseline, week 6 (middle of intervention), week 12 (EOI) and week 24 End of Study (EOS)

Study Arms (2)

Cardiopulmonary Rehabilitation (Exercise Intolerance)

EXPERIMENTAL

Participants assigned to Cardiopulmonary Rehabilitation will undergo a 12-week personalized cardiopulmonary rehabilitation intervention with a follow-up period of 3 months (total study duration of 6 months).

Behavioral: Personalized Cardiopulmonary Rehabilitation

Education

ACTIVE COMPARATOR

Participants in this group will receive two general education sessions at the start of the intervention with weekly phone/virtual follow-ups from site study staff.

Other: Education

Interventions

Personalized Cardiopulmonary Rehabilitation BEHAVIORAL

Participants in this group will complete 2-3 cardiopulmonary rehabilitation sessions per week, for 12 weeks, as tolerated. Rehabilitation sessions are provided by respiratory therapists, exercise physiologists, physical therapists, nurses, or others who have experience and training in either pulmonary or cardiac rehabilitation. Rehabilitation sessions (adjusted based on the participant's baseline assessment, symptoms, and progress) last about 1 hour and include education, aerobic exercise, strength, and flexibility training.

Cardiopulmonary Rehabilitation (Exercise Intolerance)

Education OTHER

Participants in this group will receive two general education sessions at the start of the intervention with weekly phone/virtual follow-ups from site study staff.

Education

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Known pre-existing postural orthostatic tachycardia syndrome, not related to SARS-CoV-2 infection
• Known uncontrolled hypertension (blood pressure \[BP\] ≥ 160/100 mmHg at rest)
• Any of the following within 4 weeks of enrollment - acute myocardial infarction, unstable angina, uncontrolled arrhythmias causing symptoms or hemodynamic compromise, acute myocarditis or pericarditis, uncontrolled acutely decompensated heart failure (acute pulmonary edema), acute pulmonary embolism, suspected dissecting aneurysm, severe hypoxemia at rest, thromboembolic event(s), any acute or chronic disorder that may affect exercise capacity or be aggravated by exercise (e.g., infection, exercise induced syncope, thyrotoxicosis, unable to cooperate)
• Score of 2 or greater for both frequency and severity for any of the first 5 questions on the Screening mDSQ-PEM AND answer of 'YES' to either item 7 or 8 on the Screening mDSQ-PEM, and response of \> 14 hours in item 9 OR Score of 3 or greater on any severity question (regardless of frequency) AND answer of 'YES' to either item 7 or 8 on the Screening mDSQ-PEM, and response of \> 14 hours in item 9 OR Any score of 3 or greater on any of the severity questions on the mDSQ-PEM 48-72 hours following the Screening ISWT test
• A selection of ≥ 8 on question 1 or ≥ 9 on question 3 of the OH Activity Scale from the mOHQ
• Engaged in purposeful moderate or greater intensity exercise with the intent to improve one's health 2 or more times per week over the 30 days prior to informed consent
• Inability to walk

Sponsors & Collaborators

• Duke University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

All sites listed under NCT06404047

Durham, North Carolina, 27710, United States

Location

Related Links

• Related Info

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome; Motor Activity

Interventions

Educational Status

Condition Hierarchy (Ancestors)

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Socioeconomic Factors; Population Characteristics

Study Officials

• Gary M Felker, MD

  Duke Clinical Research Institute

  STUDY CHAIR

• Barry Make, MD

  National Jewish Health

  STUDY CHAIR

• Lucinda Bateman, MD

  Bateman Horne Center

  STUDY CHAIR

• Janna Friedly, MD, MPH

  University of Washington

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The assessor of the primary outcome, Endurance Shuttle Walk Test (ESWT), is blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This platform protocol is designed to allocate participants into an appropriate intervention appendix based on their symptoms of exercise intolerance. Once assigned to an appendix, eligible participants are randomized in a 1:1 ratio to either the study intervention group or a control group.

Study Record Dates

• First Submitted: May 3, 2024
• First Posted: May 8, 2024
• Study Start: July 17, 2024
• Primary Completion: March 10, 2026
• Study Completion (Estimated): May 30, 2026
• Last Updated: May 7, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)